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ID PMID Title PublicationDate abstract
14597220 Kinetic analysis of the development of pancreatic lesions in mice infected with a murine r 2003 Nov Sjögren's syndrome (SjS)-like sialoadenitis and exocrine pancreatitis were induced in mice infected with LP-BM5 murine leukemia virus, which induces a severe immunodeficiency termed murine AIDS (MAIDS). All mice with MAIDS showed advancing cellular infiltration around the pancreatic ducts as well as systemic exocrinopathy. The primary target tissue of the pancreas was acinar cells, and the pancreatic islets were well preserved until a late phase of the disease. Immunofluorescence and flow cytometry demonstrated that CD4(+) T cells, Mac-1(+) cells, and B220(+) cells were major inflammatory components, and IFN-gamma and IL-10 were mainly detected on CD4(+) T and Mac-1(+) cells in the pancreas. Both Th1 and Th2 cells were found. TUNEL(+) apoptotic cells were mostly detected among pancreas-infiltrating cells. Fas ligand and TNF-alpha were also detected among pancreas-infiltrating cells, whereas Fas was rarely expressed in the pancreatic acinar cells. Thus, MAIDS mice could be valuable for analyzing the pathogenesis of autoimmune-related pancreatitis associated with SjS.
12737325 Local production of Ro/SSA and La/SSB autoantibodies in the target organ coincides with hi 2003 OBJECTIVE: To analyze Ro and La autoantibody levels in the periphery and production in the target organ in patients with Sjögren's syndrome. METHODS: The autoantibody production against the Ro and La proteins was investigated in 12 patients with Sjögren's syndrome. ELISA with recombinant antigens was used to determine levels in sera. The distribution of the antibody-producing plasma cells in the target organ was studied by immunohistochemistry using biotinylated antigens. RESULTS: All investigated patients with Sjögren's syndrome had detectable levels of Ro and La antibodies in sera, while local antibody-production in the salivary glands was restricted to patients with high antibody levels. The autoantibody-producing cells were identified at the periphery of the infiltrates and in interstitial spaces. CONCLUSIONS: The chronic inflammation of the salivary glands in Sjögren's syndrome may be a self-sustaining process promoting autoantibody production in the target organ, possibly contributing to increased serum levels of autoantibodies.
12428174 Biochemical deficiency of pyridoxine does not affect interleukin-2 production of lymphocyt 2002 Nov BACKGROUND: There is evidence that pyridoxine deficiency may alter the immune response. It is not known whether a deficiency of this vitamin is evident in subjects with primary Sjögren's syndrome (SS). OBJECTIVE: We studied whether subjects with primary SS showed a biochemical deficiency of pyridoxine, and if it is associated with abnormal production of interleukin-2 from lymphocytes stimulated in vitro with phytohemagglutinin (PHA). DESIGN: Two studies were conducted, (i) biochemical and nutritional assessments were performed in a cross-over study in subjects with primary SS, who were supplemented with 25 mg/day of pyridoxine or placebo for 3 months. After 1 month washout, they were supplemented for 3 months with placebo, (ii) patients with SS and matched controls received pyridoxine or placebo for 45 days, and a blood sample was obtained to study IL-2 production and expression in T-lymphocytes stimulated with PHA. RESULTS: Subjects with primary SS showed limited dietary intake of pyridoxine and biochemical deficiency of this vitamin assessed through the activation coefficient of the erythrocyte aspartate aminotransferase. The biochemical deficiency did not affect production nor mRNA expression of IL-2 from T-lymphocytes stimulated in vitro with PHA compared with the control group. Supplementation of subjects with primary SS with 25 mg/day with pyridoxine for 45 days did not produce any significant change as compared to those patients supplemented with placebo. CONCLUSIONS: Subjects with primary SS showed biochemical deficiency of pyridoxine, possibly due to limited intake of this vitamin which was corrected by supplementation with pyridoxine. However, IL-2 production and mRNA expression from stimulated lymphocytes were unaffected by supplementation, probably because the deficiency was not severe enough to affect the immune system. SPONSORSHIP: This work was supported by the National Council of Science and Technology (CONACYT), Mexico, grant no. 212226-5-0902PM.
15573866 Sigma receptor ligands: applications in inflammation and oncology. 2004 Nov Sigma (sigma) receptors were initially proposed as a subtype of opiate receptors, and bind several psychoactive compounds. They are classified into sigma 1 (sigma1) and sigma 2 (sigma2) subtypes. The characterization of these subunits, and the discovery of new specific sigma receptor ligands, demonstrated that sigma receptors belong to a specific entity distinct from opiate receptors. Radioligand-binding data have recently demonstrated that the sigma1 subtype is related to a sterol isomerase, which is involved in the cholesterol biosynthesis pathway, and also to another protein of unknown function, SRBP2 (SR-31747 binding-protein 2), which shares a high homology with this enzyme. This complex group of proteins also binds molecules devoid of central effect, which demonstrate potent anti-inflammatory properties, and so are potentially useful in pathologies where pro-inflammatory cytokines are involved, particularly rheumatoid arthritis, Crohn's disease or psoriasis. In addition, the two sigma receptor subtypes and their two related proteins are also expressed on tumor cells, where they could be of prognostic relevance, and their ligands could potentially be used in the detection and targeting of tumors.
15546336 An update of the HLA genomic region, locus information and disease associations: 2004. 2004 Dec The human major histocompatibility (MHC) genomic region at chromosomal position 6p21 encodes the six classical transplantation HLA genes and many other genes that have important roles in the regulation of the immune system as well as in some fundamental cellular processes. This small segment of the human genome has been associated with more than 100 diseases, including common diseases--such as diabetes, rheumatoid arthritis, psoriasis, asthma and various autoimmune disorders. The MHC 3.6 Mb genomic sequence was first reported in 1999 with the annotation of 224 gene loci. The locus and allelic information of the MHC continue to be updated by identifying newly mapped expressed genes and pseudogenes based on comparative genomics, SNP analysis and cDNA projects. Since 1999, new innovations in bioinformatics and gene-specific functional databases and studies on the MHC genes have resulted in numerous changes to gene names and better ways to update and link the MHC gene symbols, names and sequences together with function, variation and disease associations. In this study, we present a brief overview of the MHC genomic structure and the recent information that we have gathered on the MHC gene loci via LocusLink at the National Centre for Biological Information (http://www.ncbi.nih.gov/.) and the MHC genes' association with various diseases taken from publications and records in public databases, such as the Online Mendelian Inheritance in Man and the Genetic Association Database.
15454128 Polymyalgia rheumatica. 2004 Oct Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder and in the pelvic girdles and neck. In the past, PMR was considered a manifestation of giant cell arteritis (GCA) or a variant of elderly-onset rheumatoid arthritis (EORA). The current diagnostic criteria for PMR were empirically formulated by clinical experts who had studied the disease extensively. Arthroscopic, radioisotopic and magnetic resonance imaging studies all have indicated the presence of a synovitis in proximal joints and periarticular structures. The synovitis is probably responsible for the musculoskeletal symptoms in PMR. The prominence assigned to the proximal symptoms has probably overshadowed the less well recognized and more variable distal musculoskeletal manifestations which are present in about half of the cases. A normal erythrocyte sedimentation rate does not exclude a diagnosis of PMR. C-reactive protein and interleukin-6 seem to be more sensitive indicators of disease activity both at diagnosis and during relapse/recurrence. Corticosteroids are the drugs of choice for treating PMR. A course of treatment of 1-2 years is often required. However, some patients have a chronic, relapsing course and require low doses of corticosteroids for several years. Large, multicenter, double-blind, placebo-controlled studies are required to define the role of methotrexate and anti-TNF-alpha agents as corticosteroid-sparing drugs in PMR.
15303569 Validity of the disease repercussion profile in patients with systemic lupus erythematosus 2004 The Disease Repercussion Profile (DRP) was developed for use with patients with rheumatoid arthritis (RA) and has been shown to be a valid and clinically useful assessment of patient-perceived handicap. This study aimed to determine whether the Disease Repercussion Profile was also suitable for use with patients with systemic lupus erythematosus (SLE). Sixty patients with a definite diagnosis of SLE from a consultant rheumatologist were recruited into the study. They completed a series of questionnaires that assessed quality of life, depression, anxiety, attitudes towards the illness and the DRP. Results showed that patients with SLE endorsed each of the six spheres of the DRP as being frequently affected by their illness. Activity was most often endorsed. Both relationships and social activity were equally frequently adversely affected, and more often affected than the remaining spheres of finance, emotions and appearance. However, as in RA, when any area of function was affected, it was rated as very important to the individual. Indicators of quality of life were reliably related to all areas of function, as was depression and attitudes towards illness. The present study indicates that the DRP does have relevance for patients with SLE. Strong correlations between quality of life indicators, depression, attitudes towards illness and DRP subscales and total score indicate that this measure is a valid tool to assess the effect of illness on individuals with SLE.
15288003 BLyS--an essential survival factor for B cells: basic biology, links to pathology and ther 2004 Jul A paradigm shift in our understanding of autoimmune disease pathology is underway; B cells are now considered to play a central role in disease pathogenesis. Targeting B cells may prove to be an effective route for the development of novel therapeutics. BLyS, a member of the TNF family of cytokines, is an essential survival factor for B cells. Constitutive BLyS overexpression in mice leads to an autoimmune phenotype similar to lupus nephritis. Clinically, BLyS is elevated in patients with systemic autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosus. BLyS ablation results in a block of B cell development in which mature B cells are absent. BLyS binds to three receptors, BR3, TACI and BCMA. Analysis of the receptors suggests that the major pro-survival signals are mediated by BR3, while TACI is involved in negative signaling. BCMA is required for survival of long-lived plasma cells. BLyS signaling results in upregulation of anti-apoptotic bcl-2 family members. In animal models of autoimmune disease, BLyS antagonists reduce disease severity and delay disease progression. BLyS is an attractive target for antagonism in autoimmune diseases. Multiple approaches are being taken to antagonize BLyS including a fully human antibody and soluble BLyS receptors. These approaches are currently being tested in clinical trials.
15233502 The relative contribution of domains of quality of life to overall quality of life for dif 2004 Jun This study examined the contribution of the quality of life (QoL) domains physical, social and psychological functioning to the explanation of overall QoL. Various disorders may differentially affect QoL domains due to disease-specific factors and, consequently, the relationship between QoL domains and overall QoL may vary between diseases. We therefore studied this relationship for several diseases as well as the differential impact of these diseases on QoL. The present study had a cross-sectional design. We selected patients (aged 57 years and older) with one of the following eight chronic medical conditions: lung disorder, heart condition, hypertension, diabetes mellitus, back problems, rheumatoid arthritis, migraine, or dermatological disorders. The total group of respondents included 1457 patients and 1851 healthy subjects. Regression analyses showed that the domain of psychological functioning contributed to overall QoL for all disorders, whereas physical and social functioning contributed to overall QoL for some disorders. Differences were found between most patient groups and healthy subjects with respect to physical functioning; with respect to social and psychological functioning some groups differed from the healthy group. Explanations for the findings and implications for clinical practice are discussed.
15183929 A bispecific single-chain antibody fusion protein for targeted depletion of autoreactive B 2004 Jul Autoantigen-specific B cells are culprits in the pathogenesis of many autoimmune diseases either through the production of autoreactive antibodies or as very effective antigen-presenting cells. A general depletion of B cells by a CD20-specific monoclonal IgG1 antibody has recently been validated as an effective strategy for treating rheumatoid arthritis. However, general elimination of B cells can lead to immunosuppression and increased risk of infection. In search for a more specific approach, we have generated a fusion protein for the antigen-specific targeting of autoreactive B cells for re-directed lysis by resting human T lymphocytes. We describe the design, purification and characterization of MOGxanti-CD3, a single-chain bispecific antibody fusion protein recognizing B cell receptors specific for the human myelin oligodendrocyte glycoprotein (MOG) and to CD3 on human T cells. MOGxAnti-CD3 induced selective and very efficient redirected lysis of MOG-reactive B cells through freshly isolated, unstimulated human T cells. Fusions between autoantigens and an anti-CD3 single-chain antibody may be suitable to develop very specific therapeutic approaches for the selective depletion of autoreactive B cells in autoimmune diseases.
15067429 Eosinophilia in rheumatologic diseases: a prospective study of 1000 cases. 2004 Nov The role of eosinophilia in connective tissue diseases and the relationship between symptoms of rheumatic disease and eosinophilia have not been clearly established. The purpose of the present study was to explore the prevalence of eosinophilia in rheumatologic disease and determine its relationship to the symptoms. One thousand patients who applied to our rheumatology outpatient clinic between 2001 and 2002 were prospectively studied. The upper limit of normal blood eosinophil numbers was determined as 500 cells/microl of blood. A detailed history was obtained from all patients and careful physical examination was done. A negative correlation was observed between eosinophilia and dryness of the mouth, vitiligo, and fatigue (P < 0.05). Nonsteroidal anti-inflammatory drug usage correlated positively with eosinophilia, which was also statistically meaningful (P < 0.05). Twenty-six of our patients with fibromyalgia (n = 293), three of our subjects with rheumatoid arthritis who were using methotrexate (n = 182), 15 of whom who were not on methotrexate therapy, and one of the 26 with vasculitis had eosinophilia, which was not statistically significant (P > 0.05). None of the patients with scleroderma (n = 12) had eosinophilia. Eleven of the patients with gout had eosinophilia, and only one of them was using allopurinol. We conclude that eosinophilia can be seen in various rheumatologic conditions but, as corticosteroids are one of the most common medications used in collagen tissue diseases, the eosinophil numbers found may be lower than expected and eosinophilia may be more frequent than reported.
15050795 [Bronchiolitis with airflow obstruction in adults]. 2004 Apr PURPOSE: The purpose of this paper is twofold: to describe the clinical and anatomical characteristics of bronchiolitis associated with airflow obstruction in adults; to present through a clinical approach, a classification of the main aetiologies or pathological frames associated with that entity. KEY POINTS: The constrictive bronchiolitis type is the most frequently encountered. On clinical grounds, cough, crackles, and a progressive dyspnea develop usually within a few weeks. Radiological signs of bronchiolar abnormalities are best visualized on high resolution expiratory CT scan. The decrease in maximal airflows and oxygen tension is of limited amplitude and poorly reversible with bronchodilators. Diagnosis is easily performed when a causative event, or the clinical context, can be delineated: inhalation of toxic fumes, diffuse bronchiectasis, rheumatoid arthritis, lung or bone marrow transplantation. Delayed formation of bronchiectasis in the central airways is common. The treatment is not standardized; corticosteroids are usually prescribed as a first line therapy; the benefit of the addition of, or substitution with immunosuppressive drugs has not been adequately evaluated, but is, on the mean, of limited amplitude. PERSPECTIVES: Recent advances in the identification of inhaled agents toxic for the distal airways help in establishing appropriate measures of prevention. When the aetiology of the bronchiolitis cannot be suspected, extensive search of a causative agent should be performed, including microbial and mineral analysis of bronchoalveolar products. Negative results should lead to perform a surgical lung biopsy. The study of chronic rejection processes in animal models of lung transplantation, the identification of inhibitory factors of bronchiolar fibrogenesis, and the efficacy of some anti-cytokines on inflammatory processes could result in new therapeutic approaches.
15012931 Anti-cytokine Ab immune therapy: present status and perspectives. 2004 Jan 15 Allergy, autoimmunity and the pathogenesis of some chronic diseases are dependent on host innate and adaptative immune responses. Both responses are associated with abnormal cytokine production within pathologic tissues. Over the past two decades, the availability of purified cytokines and cytokine antibodies (Abs) has prompted a therapeutic approach that aims to supply neutralizing Abs against deleterious cytokines, through either passive immunization (administration of large quantities of high affinity Abs, prepared ex vivo) or active immunization (induction of specific Abs, using immunogenic cytokine derivatives). Both passive and active immunization can safely, transiently and effectively be used, as has been documented by animal experimentation and confirmed by clinical trials. Novel anti-cytokine therapeutic compounds, based on passive Ab immunization, are now available to treat rheumatoid arthritis (RA) and have been shown to help control neoangiogenesis in cancer patients. Clinical trials using Abs to treat allergic disorders are also underway. However, the induction of anti-idiotypic Abs may restrict the long-term use of anti-cytokine immunotherapy using allogenic or humanized/chimeric Abs. We propose that greater consideration should be given to active immunization protocols.
15002353 [New materials suitable for implantation--preparation for implants]. 2003 PURPOSE OF THE STUDY: Connective tissue components, particularly collagen and proteoglycan, stimulate cell proliferation and thus promote tissue regeneration. This fact was utilized to test some new implant materials, which were covered by these components, for the speed and quality of their encapsulation. MATERIAL: The materials tested included polyethylene (PE) with either a hydrophobic (HPHO) or a hydrophilic (HPHI) surface and the C-C composite. Before implantation in experimental animals, the materials were coated with a thin layer of collagen-proteoglycan copolymer. METHODS: Collagen was obtained from calf hide (ISC 40 fraction) and proteoglycan was isolated from calf cartilage with 2M GuHCl. The concentrations of elements in implant materials were assessed by the method of ESCA photoelectron spectroscopy (electron spectroscopy for chemical analysis) and, using a comparison of the values of electron binding energies at inner levels with the published ones, the chemical states of elements were identified. RESULTS: Carbon, oxygen and silicon were identified on the surface of the PE HPHI sample; carbon, oxygen, calcium, manganese and sulfur were found on the PE HPHO sample and nitrogen, oxygen and fluorine were present on the C-C composite. DISCUSSION: In our group of patients there was a small rate of rheumatoid arthritis, while in most literature these patients are predominant. In accordance with the outcomes of other authors, ASS is fraught with recurrence. ASS does not strike to fibrous capsule, like an open surgery synovectomy, and from these islands synovialis could regenerate. CONCLUSIONS: The presence of manganese and calcium on the surfaces of the materials investigated indicates the existence of a collagen-proteoglycan copolymer, which contains NH2 and COO groups derived from collagen and SO4 groups from proteoglycan. It is necessary to verify this theoretical assumption based on measurement data in a biological experiment.
14978747 Plasmid DNA electrotransfer for intracellular and secreted proteins expression: new method 2004 Feb In vivo electrotransfer is a physical method of gene delivery in various tissues and organs, relying on the injection of a plasmid DNA followed by electric pulse delivery. The importance of the association between cell permeabilization and DNA electrophoresis for electrotransfer efficiency has been highlighted. In vivo electrotransfer is of special interest since it is the most efficient non-viral strategy of gene delivery and also because of its low cost, easiness of realization and safety. The potentiality of this technique can be further improved by optimizing plasmid biodistribution in the targeted organ, plasmid structure, and the design of the encoded protein. In particular, we found that plasmids of smaller size were electrotransferred more efficiently than large plasmids. It is also of importance to study and understand kinetic expression of the transgene, which can be very variable, depending on many factors including cellular localization of the protein, physiological activity and regulation. The most widely targeted tissue is skeletal muscle, because this strategy is not only promising for the treatment of muscle disorders, but also for the systemic secretion of therapeutic proteins. Vaccination and oncology gene therapy are also major fields of application of electrotransfer, whereas application to other organs such as liver, brain and cornea are expanding. Many published studies have shown that plasmid electrotransfer can lead to long-lasting therapeutic effects in various pathologies such as cancer, blood disorders, rheumatoid arthritis or muscle ischemia. DNA electrotransfer is also a powerful laboratory tool to study gene function in a given tissue.
14973548 Is there a future for TNF promoter polymorphisms? 2004 Aug The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied -308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.
13679195 Effects of leflunomide on human cartilage. 2003 Sep Modern therapeutic approach in rheumatoid arthritis (RA) includes early use of disease-modifying anti-rheumatic drugs (DMARDs). DMARDs may influence the course of disease progression, and their introduction in early RA is recommended to limit irreversible joint damage. Among DMARDs, leflunomide and methotrexate are more utilised in pharmacological therapy. In the present work, we considered the effects of leflunomide, in comparison with those of methotrexate and to those of leflunomide-methotrexate combination on human cartilage to verify its effectiveness in arthritic disease, simulated by our experimental model. We measured in vitro the amount of glycosaminoglycans (GAGs) and the production of nitric oxide (NO) released into the culture medium of human articular cartilage treated with interleukin-1beta (IL-1beta), which promotes the cartilage destruction during articular disease. Leflunomide, in the presence of IL-1beta decreased NO production and GAGs release respect IL-1beta alone treated samples, in dose-related manner. Our results suggest that leflunomide is able to protect cartilage matrix from degradative factors induced by IL-1beta with respect to methotrexate and leflunomide-methotrexate combination.
12960494 Biomarkers in osteoarthritis. 2003 Sep PURPOSE OF REVIEW: Osteoarthritis is a chronic disease characterized by progressive destruction of articular cartilage and subchondral bone, and synovial reaction. Clinical and radiologic findings that form the basis of the diagnosis of osteoarthritis are poorly sensitive for monitoring the progression of the disease. Biologic markers reflecting quantitative and dynamic changes of joint tissue turnover represent promising adjunct tools. RECENT FINDINGS: New tissue-specific markers have been developed and include assays for type II collagen synthesis and degradation and synovitis. Prospective studies indicate that increased or decreased levels of some of these markers are associated with rapid progression of joint destruction in patients with knee osteoarthritis. Because progression of joint damage is likely to result primarily from an imbalance between degradation and reparative processes, a combination of markers reflecting these two components appears promising. For example, combining two new markers for type II collagen synthesis and degradation in an uncoupling index of cartilage turnover was more effective in predicting 1-year radiologic progression in knee osteoarthritis than the measurement of a single marker. Preliminary data in rheumatoid arthritis show a rapid response of a marker of type II collagen degradation under disease-modifying antirheumatic drugs, with early changes of this marker being predictive of long-term radiologic progression. SUMMARY: Recent evidence suggests that the combination of some biologic markers will be useful for identifying patients at risk for rapid joint destruction in osteoarthritis. Because of their rapid changes under treatment, biologic markers will play an important role in the development and monitoring of new structure-modifying therapies for osteoarthritis.
12768076 Azathioprine hypersensitivity: report of two cases and review of the literature. 2003 Mar Azathioprine (AZA) is a widely-used drug in the treatment of different diseases such as vasculitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel diseases and in renal transplantation. Side effects of AZA can be classified as toxic, mainly dose related (myelosuppression and hepatotoxicity) and idiosyncratic, mainly dose independent. While the toxic effects are common and well documented, the hypersensitivity reactions are rare and it is not often easy to distinguish them from systemic sepsis or disease recurrence. We report two cases of AZA hypersensitivity occurring in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis each mimicking a vasculitis relapse or a septic complication of immunosuppression, as well as a review of the literature.
12746451 Pulmonary inflammation and edema induced by phospholipase A2: global gene analysis and eff 2003 Aug 15 Victims of snakebite quickly succumb to severe respiratory failure, which can be fatal if left untreated. One of the most toxic components of snake venom is phospholipase A2 (PLA2; EC 3.1.1.4). PLA2 isolated from the elapid, Naja sputatrix, induced pulmonary inflammation and edema when administered intravenously and intratracheally to rats. Analysis of pulmonary gene expression profiles using oligonucleotide microarrays revealed 60 genes whose expression was altered by at least 3-fold in response to intratracheal instillation of PLA2 for 3 h as compared with controls. In addition to genes encoding cytokines and chemokines responsible for inflammatory processes, the Na+/K+-ATPase gene has been found to be involved in edema formation. Real-time PCR, Western blot, and immunohistochemical analyses confirmed that the expression of AQP1 and AQP5 mRNAs and proteins was decreased. Besides providing an experimental model for studies on the pathophysiology of the lung, this investigation yields a clue to the mechanisms by which endogenous PLA2s could mediate inflammation in conditions such as allergy and rheumatoid arthritis.